title: Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord.
abstract: OBJECTIVE
  Novel therapeutic interventions aimed at myelin repair are now under development for neuroprotection as well as functional recovery of patients with multiple sclerosis. However, development of myelin repair therapy necessitates a noninvasive approach for measuring changes in myelin content in vivo in a quantitative fashion not yet possible using magnetic resonance imaging. For this reason, we developed a novel positron emission tomography (PET) probe, termed [11C]MeDAS, that is capable of longitudinally imaging central nervous system myelin content.
  
  
  METHODS
  The binding properties of [11C]MeDAS for myelin were systematically evaluated by in vitro and in situ fluorescent staining of the spinal cord and the brain, and by in vivo competitive blocking studies. Longitudinal PET studies were conducted in 3 rat models involving acute focal neuroinflammation in the brain, lysophosphatidylcholine (LPC)-induced focal demyelination in the spinal cord, and experimental autoimmune encephalomyelitis (EAE). Image-guided myelin repair therapy was conducted in an LPC rat model using a mesenchymal stem cell-based hepatocyte growth factor (HGF). Biodistribution and acute toxicity studies of [11C]MeDAS were also conducted.
  
  
  RESULTS
  MeDAS selectively stains myelin in the spinal cord and brain. Neuroinflammation did not affect [11C]MeDAS uptake in the brain as long as the myelin sheaths remained intact. Longitudinal PET studies in LPC and EAE rat models demonstrate that [11C]MeDAS uptake changes correlate with associated myelin loss in the spinal cord. Furthermore, using [11C]MeDAS-PET, the efficacy of myelin repair therapy with HGF was longitudinally monitored in vivo.
  
  
  CONCLUSIONS
  [11C]MeDAS-PET is a promising imaging marker for monitoring myelin pathology in vivo, future applications of which in humans should be achievable.
authors.affiliation: Division of Radiopharmaceutical Science, Case Center for Imaging Research Department of Radiology, Case Western Reserve University, Cleveland, OH.
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baeslack
authors.forename: Anita
authors.initials: A
authors.lastname: Zaremba
authors.forename: Jordan
authors.initials: J
authors.lastname: Hecker
authors.forename: Janet
authors.initials: J
authors.lastname: Kraso
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D009186:Myelin Sheath / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000000981:diagnostic imaging* / Q000473:pathology